FP18-6 Endoluminal Sleeve Implantation Delays the Onset of Severe Diabetes in Zdf Rats

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP18-Diabetes: Glycemia & Insulin Sensitivity
Basic/Clinical
Sunday, June 16, 2013: 10:45 AM-11:15 AM
Presentation Start Time: 11:10 AM
Room 304 (Moscone Center)

Poster Board SUN-784
Yarong Lu*, Kimmo T Jokivarsi, Hansoo Yang, Philip Davis, Anna-Liisa Brownell and Lee M Kaplan
Massachusetts General Hospital and Harvard Medical School, Boston, MA
Noninvasive and reversible endoluminal sleeve (ELS) implantation mimics the effects of Duodenal–jejunal bypass (DJB) without the risks associated with surgery. Our previous studies suggested that ELS induces weight loss and improved glucose homeostasis in diet-induced obese rats. To test the effect of ELS on lost-compensatory diabetic status, we choose Zucker diabetic fatty (ZDF) rats, an obese type 2 diabetes model with both insulin resistance and impaired beta-cell mass. Two-month-old male fa/fa (obese) rats were fed with Labdiet 5008 to induce the programmed development of diabetes in this model. Different lengths of ELS were implanted into ZDF obese rats at the starting point of duodenum and covered either the duodenum alone (ELS-D; 6cm) or the duodenum and proximal jejunum (ELS-D/J, 12cm). The localization of implanted ELS inside the intestine was detected by MicroCT scanning. To our surprise, neither length of ELS implantation changed body weight in the ZDF obese rats, but both significantly decreased 40% fasting blood glucose level compared with sham controls. Oral glucose tolerance tests suggested maintained glucose-stimulated insulin secretion in the ELS implanted animals, compared with loss of this response in sham controls. ELS implantation didn't affect serum leptin levels in those rats. Immunofluorescence staining of pancreatic tissue revealed preserved islet insulin staining in ELS implanted rats, which was consistent with the two-fold increased insulin content of these samples. Immunohistochemistry revealed thickened intestine wall and longer villi in the region of small intestine covered by the ELS. These studies suggest that endoluminal sleeve implantation delays the onset of severe hyperglycemia and preserves pancreatic insulin production independent of weight lost in Zucker Diabetic Fatty rats. Similar results after both ELS-D and ELS-D/J implanted groups suggest a crucial role of the duodenum alone in regulating pancreatic beta-cell function. Our results provide us a clue for searching novel anti-diabetic factors from the intestine.

Aguirre V et al. Obesity (Silver Spring). 2008 Dec;16(12):2585-92.

Nothing to Disclose: YL, KTJ, HY, PD, ALB, LMK

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: NIH Grant 1RC2DK088661-01 awarded to Dr. Lee M. Kaplan.
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